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https://www.readbyqxmd.com/read/30557817/identification-of-novel-pi3k%C3%AE-inhibitors-by-docking-admet-prediction-and-molecular-dynamics-simulations
#1
Ya-Ya Liu, Xiao-Yan Feng, Wen-Qing Jia, Zhi Jing, Wei-Ren Xu, Xian-Chao Cheng
BACKGROUND: Phosphoinositide-3-kinase Delta (PI3Kδ) plays a key role in B-cell signal transduction and inhibition of PI3Kδ is confirmed to have clinical benefit in certain types of activation of B-cell malignancies. Virtual screening techniques have been used to discover new molecules for developing novel PI3Kδ inhibitors with little side effects. METHOD: Computer aided drug design method were used to rapidly screen optimal PI3Kδ inhibitors from the Asinex database...
December 7, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/30557761/chronic-stress-exposure-and-daily-stress-appraisals-relate-to-biological-aging-marker-p16-ink4a
#2
Kelly E Rentscher, Judith E Carroll, Rena L Repetti, Steve W Cole, Bridget M Reynolds, Theodore F Robles
Previous research has linked exposure to adverse social conditions with DNA damage and accelerated telomere shortening, raising the possibility that chronic stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether these stress-related effects extend to additional hallmarks of biological aging, including cellular senescence, a stable state of cell cycle arrest. The present study aimed to investigate associations between psychosocial stress and two markers of cellular aging-leukocyte telomere length (LTL) and cellular senescence signal p16INK4a ...
December 7, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/30557701/the-intestinal-lymphatic-system-functions-and-metabolic-implications
#3
REVIEW
Vincenza Cifarelli, Anne Eichmann
The lymphatic system of the gut plays important roles in the transport of dietary lipids, as well as in immunosurveillance and removal of interstitial fluid. Historically, despite its crucial functions in intestinal homeostasis, the lymphatic system has been poorly studied. In the last two decades, identification of specific molecular mediators of lymphatic endothelial cells (LECs) growth together with novel genetic approaches and intravital imaging techniques, have advanced our understanding of the mechanisms regulating intestinal lymphatic physiology in health and disease...
December 14, 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30557630/kit-as-a-therapeutic-target-for-non-oncological-diseases
#4
REVIEW
Asuncion Martinez-Anton, Delphine Gras, Arnaud Bourdin, Patrice Dubreuil, Pascal Chanez
KIT is a receptor tyrosine kinase that after binding to its ligand stem cell factor activates signaling cascades linked to biological processes such as proliferation, differentiation, migration and cell survival. Based on studies performed on SCF and/or KIT mutant animals that presented anemia, sterility, and/or pigmentation disorders, KIT signaling was mainly considered to be involved in the regulation of hematopoiesis, gametogenesis, and melanogenesis. More recently, novel animal models and ameliorated cellular and molecular techniques have led to the discovery of a widen repertoire of tissue compartments and functions that are being modulated by KIT...
December 14, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30557124/the-effect-of-biologic-agents-on-bone-homeostasis-in-chronic-inflammatory-rheumatic-diseases
#5
REVIEW
Ombretta Di Munno, Francesco Ferro
Osteoporosis (OP) and increased fracture risk are widely observed comorbidities in chronic inflammatory rheumatic diseases (CIRDs). Improved knowledge of the immune/inflammatory pathways, which characterise the pathophysiology of rheumatoid arthritis (RA) and seronegative spondyloarthropathies (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have provided the link between inflammation and bone loss, via a complex network of bone cells, T and B cells, pro-inflammatory cytokines such as TNF-α, IL1, IL6, IL17, IL23, costimulator molecules, signalling pathways including both RANKL/RANK/OPG and Wnt signallings...
November 19, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/30557063/reversibility-of-castration-resistance-status-after-radium-223-dichloride-treatment-clinical-evidence-and-review-of-the-literature
#6
Maria Ricci, Viviana Frantellizzi, Nadia Bulzonetti, Giuseppe De Vincentis
PURPOSE: In the history of prostate cancer, some of patients progresses to castration resistant prostate cancer (CRPC) stage and, although new drugs and treatment protocols have been introduced, CRPC presents poor prognosis. This review focused on biological mechanisms, underlying CRPC described in scientific literature in order to explain the reversion of resistance to castration. We present the case of a 73 years-old man, affected by bone metastatic CRPC, early treated with Radium-223 with a complete response...
December 17, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/30556925/loss-of-nfat2-expression-results-in-the-acceleration-of-clonal-evolution-in-chronic-lymphocytic-leukemia
#7
David J Müller, Stefan Wirths, Alexander R Fuchs, Melanie Märklin, Jonas S Heitmann, Marc Sturm, Michael Haap, Andreas Kirschniak, Yoshiteru Sasaki, Lothar Kanz, Hans-Georg Kopp, Martin R Müller
Chronic lymphocytic leukemia (CLL) can be defined as a clonal expansion of B cells with stereotypic BCRs. Somatic hypermutation of the BCR heavy chains (IGVH) defines a subgroup of patients with a better prognosis. In up to 10% of CLL cases, a transformation to an aggressive B cell lymphoma (Richter's syndrome) with a dismal prognosis can be observed over time. NFAT proteins are transcription factors originally identified in T cells, which also play an important role in B cells. The TCL1 transgenic mouse is a well-accepted model of CLL...
December 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/30556883/mir-212-5p-regulates-the-proliferation-and-apoptosis-of-aml-cells-through-targeting-fzd5
#8
J-F Lin, H Zeng, J-Q Zhao
OBJECTIVE: To explore the effects of microRNA-212-5p (miR-212-5p) on biological functions of acute myeloid leukemia (AML) and to find the potential molecular mechanism. PATIENTS AND METHODS: We measured the expression level of miR-212-5p in 35 AML patients and 20 patients with idiopathic thrombocytopenic purpura (ITP) as control cases. Besides, the miR-212-5p expression at cellular level was checked as well. In order to screen the functional targets of miR-212-5p, online prediction software was used and gene frizzled class receptor 5 (FZD5) attracted our attention...
December 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30556882/upregulation-of-long-noncoding-rna-mrccat1-predicts-poor-prognosis-and-functions-as-an-oncogene-in-glioma
#9
J Ma, L-J Su, Z-J Zheng
OBJECTIVE: This study aimed to investigate the expressions, clinical significances, roles, and mechanism of action of MRCCAT1 in glioma. PATIENTS AND METHODS: The expression of MRCCAT1 in 103 glioma tissues with different grades and 21 normal brain tissues was measured by qPCR. The prognostic value of MRCCAT1 was investigated by Kaplan-Meier survival analysis. The biological roles of MRCCAT1 on glioma cell proliferation were assessed by Glo cell viability assays and ethynyl deoxyuridine incorporation assays...
December 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30556871/increased-expression-of-lncrna-fth1p3-promotes-oral-squamous-cell-carcinoma-cells-migration-and-invasion-by-enhancing-pi3k-akt-gsk3b-wnt-%C3%AE-catenin-signaling
#10
M Liu, X Gao, C-L Liu
OBJECTIVE: Growing evidence indicated that long noncoding RNAs (lncRNAs) played important roles in tumor initiation and progression. In this study, we aimed to investigate the expression pattern, clinical significance, and biological function of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: We evaluated the expression levels of FTH1P3 in OSCC tissues, adjacent normal tissues and cells with quantitative Real-time polymerase chain reaction...
December 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30556869/long-non-coding-rna-linc00675-inhibits-tumorigenesis-and-emt-via-repressing-wnt-%C3%AE-catenin-signaling-in-esophageal-squamous-cell-carcinoma
#11
Y-B Zhong, A-J Shan, W Lv, J Wang, J-Z Xu
OBJECTIVE: Long noncoding RNA LINC00675 (LINC00675) seems to play an anti-oncogenic role in cancers, though its exact function remains unknown. Up to date, little is known about the role of LINC00675 in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to explore the expression pattern, clinical significance and biological function of LINC00675 in ESCC. PATIENTS AND METHODS: RT-PCR was performed to detect the expression levels of LINC00675 in both ESCC tissue and cell lines...
December 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30556859/circmto1-inhibits-cell-proliferation-and-invasion-by-regulating-wnt-%C3%AE-catenin-signaling-pathway-in-colorectal-cancer
#12
Z Ge, L-F Li, C-Y Wang, Y Wang, W-L Ma
OBJECTIVE: Circular RNAs (circRNAs) play critical roles in disease incidence. However, the roles of circRNAs in colorectal cancer (CRC) progression remain largely unknown. We explored the expression of circMTO1 in CRC and elucidated the underlying molecular mechanisms. PATIENTS AND METHODS: Quantitative Real-time-PCR (qRT-PCR) was used to explore circMTO1 expression in CRC tissues and cell lines. The effect of circMTO1 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) assay, Edu assay, colony formation assay, wound-healing assay and transwell invasion assay...
December 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30556811/genome-wide-interrogation-of-extracellular-vesicle-biology-using-barcoded-mirnas
#13
Albert Lu, Paulina Wawro, David W Morgens, Fernando Portela, Michael C Bassik, Suzanne R Pfeffer
Extracellular vesicles mediate transfer of biologically active molecules between neighboring or distant cells, and these vesicles may play important roles in normal physiology and the pathogenesis of multiple disease states including cancer. However, the underlying molecular mechanisms of their biogenesis and release remain unknown. We designed artificially barcoded, exosomal microRNAs (bEXOmiRs) to monitor extracellular vesicle release quantitatively using deep sequencing. We then expressed distinct pairs of CRISPR guide RNAs and bEXOmiRs, enabling identification of genes influencing bEXOmiR secretion from Cas9-edited cells...
December 17, 2018: ELife
https://www.readbyqxmd.com/read/30556575/algae-metabolites-from-in-vitro-growth-inhibitory-effects-to-promising-anticancer-activity
#14
REVIEW
Florence Lefranc, Aikaterini Koutsaviti, Efstathia Ioannou, Alexander Kornienko, Vassilios Roussis, Robert Kiss, David Newman
Covering: 1957 to 2017Algae constitute a heterogeneous group of eukaryotic photosynthetic organisms, mainly found in the marine environment. Algae produce numerous metabolites that help them cope with the harsh conditions of the marine environment. Because of their structural diversity and uniqueness, these molecules have recently gained a lot of interest for the identification of medicinally useful agents, including those with potential anticancer activities. In the current review, which is not a catalogue-based one, we first highlight the major biological events that lead to various types of cancer, including metastatic ones, to chemoresistance, thus to any types of current anticancer treatment relating to the use of chemotherapeutics...
December 17, 2018: Natural Product Reports
https://www.readbyqxmd.com/read/30556357/anti-inflammatory-effect-of-novel-7-substituted-coumarin-derivatives-through-inhibition-of-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Chaoyu Mu, Mingfei Wu, Zeng Li
A series of novel 7-substituted coumarin derivatives was synthesized and evaluated. Biological screening results obtained by the evaluation of the compounds' inhibition against LPS-induced IL-6 and TNF-α release in RAW 264.7 cells indicated that most compounds exhibited potent anti-inflammatory activity. Among them, compound 2d showed the best activity. The potential targets of title compound 2d were reverse screened with the molecular modeling software-Discovery Studio 2017 R2. Screening and molecule docking results showed that 2d may bind the active site (NLS Polypeptide) of NF-κB p65, and this binding affinity was confirmed by surface plasmon resonance (SPR)analysis...
December 16, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/30555993/raman-spectroscopic-analysis-of-signaling-molecules-dopamine-receptors-interactions-in-living-cells
#16
Achut P Silwal, H Peter Lu
The selective interaction of signaling compounds including neurotransmitters and drugs with the dopamine receptors (DARs) is extremely important for the treatment of neurodegenerative diseases. Here, we report a method to probe the selective interactions of signaling compounds with D1 and D2 DARs in living cells using the combined approach of theoretical calculation and surface-enhanced Raman spectroscopy (SERS). When signaling compounds such as DA, amphetamine, methamphetamine, and methylenedioxypyrovalerone interact with D1 dopamine receptors (DRD1), the intracellular cyclic adenosine monophosphate (cAMP) level is increased...
November 30, 2018: ACS Omega
https://www.readbyqxmd.com/read/30555990/label-free-whole-cell-biosensing-for-high-throughput-discovery-of-activators-and-inhibitors-targeting-g-protein-activated-inwardly-rectifying-potassium-channels
#17
Katrin M Krebs, Eva M Pfeil, Katharina Simon, Manuel Grundmann, Felix Häberlein, Oscar M Bautista-Aguilera, Michael Gütschow, C David Weaver, Bernd K Fleischmann, Evi Kostenis
Dynamic mass redistribution (DMR) and cellular dielectric spectroscopy (CDS) are label-free biosensor technologies that capture real-time integrated cellular responses upon exposure to extra- and intracellular stimuli. They register signaling routes that are accompanied by cell shape changes and/or molecular movement of cells proximal to the biosensor to which they are attached. Here, we report the unexpected observation that robust DMR and CDS signatures are also elicited upon direct stimulation of G protein-activated inwardly rectifying potassium (GIRK) channels, which are involved in the regulation of excitability in the heart and brain...
November 30, 2018: ACS Omega
https://www.readbyqxmd.com/read/30555805/immune-cell-counts-and-signaling-in-body-fluids-of-cows-vaccinated-against-clostridium-difficile
#18
Christiane Schmautz, Nadine Müller, Marlene Auer, Ines Ballweg, Michael W Pfaffl, Heike Kliem
Background: New treatment options are needed to prevent relapses following failed antibiotic therapies of Clostridium difficile infections (CDI) in humans. The concomitant therapy with an anti- C. difficile IgA containing whey protein concentrate can support the sustainable recovery of CDI patients. For 31 weeks, nine dairy cows were continuously vaccinated with several anti- C. difficile vaccines by certain routes of administration to produce anti- C. difficile IgA enriched milk. The study aimed at finding decisive differences between low responder (LR) and high responder (HR) cows (> 8...
December 2018: Journal of Biological Research
https://www.readbyqxmd.com/read/30555637/water-transport-proteins-aquaporins-aqps-in-cancer-biology
#19
REVIEW
Salah Dajani, Anand Saripalli, Neelam Sharma-Walia
As highly conserved ubiquitous proteins, aquaporins (AQPs) play an imperative role in the development and progression of cancer. By trafficking water and other small molecules, AQPs play a vital role in preserving the cellular environment. Due to their critical role in cell stability and integrity, it would make sense that AQPs are involved in cancer progression. When AQPs alter the cellular environment, there may be several downstream effects such as alterations in cellular osmolality, volume, ionic composition, and signaling pathways...
November 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/30555578/a-positive-feedback-loop-of-slp2-activates-mapk-signaling-pathway-to-promote-gastric-cancer-progression
#20
Wenhui Ma, Zhuoluo Xu, Yutian Wang, Wenyi Li, Zhigang Wei, Tao Chen, Tingyu Mou, Mingzhen Cheng, Jun Luo, Tingyue Luo, Yuehong Chen, Jiang Yu, Weijie Zhou, Guoxin Li
Rationale: This study is to validate the clinicopathologic significance and potential prognostic value of SLP2 in gastric cancer (GC), to investigate the biological function and regulation mechanism of SLP2, and to explore potential therapeutic strategies for GC. Methods: The expression of SLP2 in GC tissues from two cohorts was examined by IHC. The biological function and regulation mechanism of SLP2 and PHB was validated via loss-of-function or gain-of-function experiments. In vitro proliferation detection was used to evaluate the therapeutic effects of Sorafenib...
2018: Theranostics
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